Applied Evidence

Combatting the cough that won’t quit

Author and Disclosure Information

By the time patients come to see you, they’ve often tried a host of OTC remedies. This review and handy algorithm will help you detect and treat the cause of persistent cough without delay.




Always include postnasal drip, asthma, and gastroesophageal reflux disease in the differential diagnosis for persistent cough, regardless of clinical signs and symptoms. B

Do not rely on a patient’s description of the character and timing of the cough or the absence (or presence) of sputum to narrow down the differential diagnosis. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

CASE Margaret M, a 52-year-old nonsmoker, came to our clinic because of a persistent cough that had started about 4 weeks earlier. She had tried multiple over-the-counter cough suppressants, including dextromethorphan and guaifenesin, as well as cough drops, but none had been effective.

Margaret denied having had a cold or respiratory infection in the past few months or being in close contact with anyone with a chronic cough, and she had never had an asthma diagnosis. In response to a question about previous coughing episodes, the patient recalled having had several bouts of chronic cough in the past, including one about a year ago.

While Margaret had no known allergies, she did have occasional heartburn, which an antacid—or, at times, a drink of water—always relieved. Thyroid medication and calcium were the only things she took on a regular basis, separated by several hours to avoid problems with absorption.

Patients like Margaret, who seek help from their primary care physician only after attempting to combat a persistent cough on their own, may be quite frustrated by the time they arrive in your office. They’re counting on you to provide a cure. Fortunately, you’re likely to find it, as the differential diagnosis for subacute cough (a cough of 3-8 weeks’ duration) is limited.

Nonetheless, finding the cause of a subacute or chronic cough (lasting >8 weeks) is sometimes a matter of trial and error. Postnasal drip (also known as upper airway cough syndrome, or UACS), asthma, and gastroesophageal reflux disease (GERD) are the most common causes,1,2 followed by postinfectious cough, nonasthmatic eosinophilic bronchitis (NAEB), and pertussis.3 Although these conditions are all relatively well known, they are not always easy to detect: Some disorders, including UACS, asthma, and GERD, may be “silent,” with persistent cough the only presenting sign or symptom.4 In other cases, more than one condition may be contributing to the cough.

Starting with trials of empiric therapy for the most common causes of persistent cough—with sequential therapy and diagnostic tests, as needed—is far more effective than searching for relatively uncommon or obscure conditions. Following such a protocol, as detailed in the algorithm (FIGURE)4-7 we’ve developed and in the text that follows, can help you combat subacute and chronic cough in a cost-effective, timely way.

Dx and treatment when persistent cough is the only symptom4-7

*May include CXR, PPD, B pertussis IgG or IgA, spirometry with methacholine inhalation challenge, barium swallow, prolonged pH monitoring, sinus CT, and sputum eosinophil count, excluding any tests that have already been performed.
ACEI, angiotensin-converting enzyme inhibitor; CT, computed tomography; COPD, chronic obstructive pulmonary disease; CXR, chest x-ray; GERD, gastroesophageal reflux disease; IgA, immunoglobulin A; IgG, immunoglobulin G; PND, postnasal drip; PPD, purified protein derivative; PPI, proton pump inhibitor.

Treat all patients for upper airway cough syndrome

Postnasal drip—renamed UACS by the guideline committee of the American Association of Chest Physicians because it isn’t clear whether the cough is caused by irritation from direct contact with postnasal drip or by inflammation of cough receptors in the upper airway—is the most common cause of chronic cough.6

The differential diagnosis for UACS, which is implicated in about 34% of cases of persistent cough, includes allergic, postinfectious, and occupational rhinitis; rhinitis due to anatomic abnormalities or physical or chemical irritants, rhinitis medicamentosa, and rhinitis of pregnancy; bacterial sinusitis; and allergic fungal sinusitis.8

The signs and symptoms of UACS are nonspecific, and a definitive diagnosis typically cannot be made from the medical history and physical examination alone. What’s more, the absence of any of the usual clinical findings—eg, rhinorrhea and excess sputum production—should not preclude an empiric trial with a first-generation antihistamine-decongestant combination such as brompheniramine/sustained-release pseudoephedrine. Second-and third-generation combination products, such as fexofenadine/pseudoephedrine, should not be used, as they are not effective in treating UACS.4


Next Article: